Effect of simultaneous integrated boost concepts on photoneutron and distant out-of-field doses in VMAT for prostate cancer.

BACKGROUND: A simultaneous integrated boost (SIB) may result in increased out-of-field (DOOF) and photoneutron (HPN) doses in volumetric modulated arc therapy (VMAT) for prostate cancer (PCA). This work therefore aimed to compare DOOF and HPN in flattened (FLAT) and flattening filter-free (FFF) 6­MV and 10-MV VMAT treatment plans with and without SIB. METHODS: Eight groups of 30 VMAT plans for PCA with 6 MV or 10 MV, with or without FF and with uniform (2 Gy) or SIB target dose (2.5/3.0 Gy) prescriptions (CONV, SIB), were generated. All 240 plans were delivered on a slab-phantom and compared with respect to measured DOOF and HPN in 61.8 cm distance from the isocenter. The 6­ and 10-MV flattened VMAT plans with conventional fractionation (6- and 10-MV FLAT CONV) served as standard reference groups. Doses were analyzed as a function of delivered monitor units (MU) and weighted equivalent square field size Aeq. Pearson's correlation coefficients between the presented quantities were determined. RESULTS: The SIB plans resulted in decreased HPN over an entire prostate RT treatment course (10-MV SIB vs. CONV -38.2%). Omission of the flattening filter yielded less HPN (10-MV CONV -17.2%; 10-MV SIB -22.5%). The SIB decreased DOOF likewise by 39% for all given scenarios, while the FFF mode reduced DOOF on average by 60%. A strong Pearson correlation was found between MU and HPN (r > 0.9) as well as DOOF (0.7 < r < 0.9). CONCLUSION: For a complete treatment, SIB reduces both photoneutron and OOF doses to almost the same extent as FFF deliveries. It is recommended to apply moderately hypofractionated 6­MV SIB FFF-VMAT when considering photoneutron or OOF doses.

Epidemiology and Clinical Outcomes of Community-Acquired Acute Kidney Injury in the Emergency Department: A Multisite Retrospective Cohort Study.

RATIONALE & OBJECTIVE: The prevalence of community-acquired acute kidney injury (CA-AKI) in the United States and its clinical consequences are not well described. Our objective was to describe the epidemiology of CA-AKI and the associated clinical outcomes. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 178,927 encounters by 139,632 adults at 5 US emergency departments (EDs) between July 1, 2017, and December 31, 2022. PREDICTORS: CA-AKI identified using KDIGO (Kidney Disease: Improving Global Outcomes) serum creatinine (Scr)-based criteria. OUTCOMES: For encounters resulting in hospitalization, the in-hospital trajectory of AKI severity, dialysis initiation, intensive care unit (ICU) admission, and death. For all encounters, occurrence over 180 days of hospitalization, ICU admission, new or progressive chronic kidney disease, dialysis initiation, and death. ANALYTICAL APPROACH: Multivariable logistic regression analysis to test the association between CA-AKI and measured outcomes. RESULTS: For all encounters, 10.4% of patients met the criteria for any stage of AKI on arrival to the ED. 16.6% of patients admitted to the hospital from the ED had CA-AKI on arrival to the ED. The likelihood of AKI recovery was inversely related to CA-AKI stage on arrival to the ED. Among encounters for hospitalized patients, CA-AKI was associated with in-hospital dialysis initiation (OR, 6.2; 95% CI, 5.1-7.5), ICU admission (OR, 1.9; 95% CI, 1.7-2.0), and death (OR, 2.2; 95% CI, 2.0-2.5) compared with patients without CA-AKI. Among all encounters, CA-AKI was associated with new or progressive chronic kidney disease (OR, 6.0; 95% CI, 5.6-6.4), dialysis initiation (OR, 5.1; 95% CI, 4.5-5.7), subsequent hospitalization (OR, 1.1; 95% CI, 1.1-1.2) including ICU admission (OR, 1.2; 95% CI, 1.1-1.4), and death (OR, 1.6; 95% CI, 1.5-1.7) during the subsequent 180 days. LIMITATIONS: Residual confounding. Study implemented at a single university-based health system. Potential selection bias related to exclusion of patients without an available baseline Scr measurement. Potential ascertainment bias related to limited repeat Scr data during follow-up after an ED visit. CONCLUSIONS: CA-AKI is a common and important entity that is associated with serious adverse clinical consequences during the 6-month period after diagnosis. PLAIN-LANGUAGE SUMMARY: Acute kidney injury (AKI) is a condition characterized by a rapid decline in kidney function. There are many causes of AKI, but few studies have examined how often AKI is already present when patients first arrive to an emergency department seeking medical attention for any reason. We analyzed approximately 175,000 visits to Johns Hopkins emergency departments and found that AKI is common on presentation to the emergency department and that patients with AKI have increased risks of hospitalization, intensive care unit admission, development of chronic kidney disease, requirement of dialysis, and death in the first 6 months after diagnosis. AKI is an important condition for health care professionals to recognize and is associated with serious adverse outcomes.

Unfinished business: Terminated cancer trials and the relevance of treatment intent, sponsors and intervention types.

The aim of the study was to report on the association of trial sponsors with intervention type, treatment intent, recruitment success and reasons to terminate cancer trials. The ClinicalTrials database was searched for interventional Phase 3 cancer trials (01/2006-05/2017). Noncancer studies and ongoing studies were excluded, permanently suspended studies were counted as terminated. Trials were stratified according to sponsors (industry/nonindustry), intervention type, setting (curative/palliative) and intent of intervention (curative/symptom-control/life-extending). We identified 345 terminated trials and 1137 completed studies as a control group. The frequency of premature termination did not differ significantly between sponsors. Time to termination was shorter but recruitment per month prior to termination was higher in industry-sponsored studies (7.0 vs 2.2 patients/month; P < .001). Drug interventions were more common in industry-sponsored, all other interventions in nonindustry-sponsored settings (P < .001). Life-extending palliative interventions occurred more frequently, symptom-control interventions in a curative setting less frequently in industry-sponsored trials (both P < .001). Intervention, setting and intent were not associated with termination in industry-sponsored trials. In nonindustry-sponsored trials, the frequency of drug interventions and life-extending (noncurative) interventions were increased in terminated trials (both P < .05); symptom-control interventions in curative settings occurred more frequently in completed studies. Industry-sponsored trials were more often terminated due to toxicity/inefficacy while lack of accrual occurred more frequently in nonindustry-sponsored trials (P < .01). Interventions, treatment setting/intent and reasons for termination differed between sponsor types. In nonindustry-sponsored trials, drug interventions and life-extending (noncurative) interventions were associated with premature termination and symptom-control interventions (curative setting) were associated with trial completion.

[MRI-guided minimally invasive treatment of prostate cancer]. / MRT-gestützte minimal-invasive Therapie des Prostatakarzinoms.

CLINICAL/METHODOLOGICAL ISSUE: Multiparametric magnetic resonance imaging (mpMRI) of the prostate plays a crucial role in the diagnosis and local staging of primary prostate cancer. STANDARD RADIOLOGICAL METHODS: Image-guided biopsy techniques such as MRI-ultrasound fusion not only allow guidance for targeted tissue sampling of index lesions for diagnostic confirmation, but also improve the detection of clinically significant prostate cancer. METHODOLOGICAL INNOVATIONS: Minimally invasive, focal therapies of localized prostate cancer complement the treatment spectrum, especially for low- and intermediate-risk patients. PERFORMANCE: In patients of low and intermediate risk, MR-guided, minimally invasive therapies could enable local tumor control, improved functional outcomes and possible subsequent therapy escalation. Further study results related to multimodal approaches and the application of artificial intelligence (AI) by machine and deep learning algorithms will help to leverage the full potential of focal therapies for prostate cancer in the upcoming era of precision medicine. ACHIEVEMENTS: Completion of ongoing randomized trials comparing each minimally invasive therapy approach with established whole-gland procedures is needed before minimally invasive therapies can be implemented into existing treatment guidelines. PRACTICAL RECOMMENDATIONS: This review article highlights minimally invasive therapies of prostate cancer and the key role of mpMRI for planning and conducting these therapies.

Long-term outcome after intraoperative radiotherapy as a boost in breast cancer.

PURPOSE: To investigate long-term oncological outcome and incidence of chronic side effects in patients with breast cancer and intraoperative radiotherapy given as an upfront boost (IORT boost). METHODS: Retrospective analysis of 400 patients with an IORT boost with low-energy X­rays (20 Gy), subsequent whole-breast irradiation (46-50 Gy), and annual oncological follow-up. Side effects were prospectively evaluated (LENT-SOMA scales) over a period of up to 15 years. Side effects scored ≥grade 2 at least three times during follow-up were judged to be chronic. RESULTS: The median age was 63 years (30-85) and the median follow-up was 78 months (2-180) after IORT boost. In 15 patients a local recurrence occurred, resulting in a local recurrence rate at 5, 10, and 15 years of 2.0%, 6.6%, and 10.1%, respectively. The overall survival rates at 5, 10, and 15 years were 92.1%, 81.8%, and 80.7%, respectively. The most common high-grade side effects were fibrosis (21%) and pain (8.6%). The majority of side effects occurred within the first 3 years. The actuarial rates of chronic fibrosis were 19.1% and 21.1% at 5 and ≥8 years, of chronic pain 8.6% at ≥4 years, of chronic edema of the breast 2.4% at ≥2 years, of chronic lymphedema 0.0% at 5 and 10 years, and of chronic hyperpigmentation 0.5% at ≥2 years. Side effects were similar or less than expected from an external beam boost. CONCLUSION: IORT boost appears to be a highly efficient and safe method for upfront delivery of the tumor bed boost in high-risk breast cancer patients.

Risk of Acute Kidney Injury Associated With Medication Administration in the Emergency Department.

BACKGROUND: Patients who develop acute kidney injury (AKI) have a 2-fold increased risk for major adverse events within 1 year. An estimated 19-26% of all cases of hospital-acquired AKI may be attributable to drug-induced kidney disease (DIKD). Patients evaluated in the emergency department (ED) are often prescribed potentially nephrotoxic drugs, yet the role of ED prescribing in DIKD is unknown. OBJECTIVE: We sought to measure the association between ED medication administration and development of AKI. METHODS: This was a retrospective 5-year cohort analysis at a single center. Patients with a serum creatinine measurement at presentation in the ED and 24-168 h later were included. Outcome was incidence of AKI as defined by Kidney Disease Improving Global Outcomes criteria in the 7 days after ED evaluation. Medication administration risk was estimated using Cox proportional hazards model. RESULTS: There were 46,965 ED encounters by 30,407 patients included in the study, of which 6461 (13.8%) patients met the criteria for AKI. For hospitalized patients, administration of a potentially nephrotoxic medication was associated with increased risk of AKI (hazard ratio [HR] 1.30 [95% confidence interval {CI} 1.20-1.41]). Diuretics were associated with the largest risk of AKI (HR 1.64 [95% CI 1.52-1.78]), followed by angiotensin-converting enzyme inhibitors (HR 1.39 [95% CI 1.26-1.54]) and antibiotics (HR 1.13 [95% CI 1.05-1.22]). For discharged patients, administration of antibiotics was strongly associated with increased risk of AKI (HR 3.19 [95% CI 1.08-9.43]). CONCLUSION: ED administration of potentially nephrotoxic medications was associated with an increased risk of AKI in the following 7 days. Diuretics, angiotensin-converting enzyme inhibitors, and antibiotics were independently associated with increased risk of AKI. Nephroprotective practices in the ED may mitigate kidney injury and long-term adverse outcomes.

Single-center long-term results from the randomized phase-3 TARGIT-A trial comparing intraoperative and whole-breast radiation therapy for early breast cancer.

PURPOSE: Partial breast irradiation using intraoperative radiotherapy (IORT) after breast-conserving surgery could be sufficient for a selected group of breast cancer patients. We report the results of a cohort of patients from a single center treated as part of the randomized phase-3 TARGIT-A trial. METHODS: Patients (≥50 years) with cT1 cN0 cM0 and invasive ductal histology on biopsy were randomized between IORT with 20 Gy (arm-A) or postoperative whole-breast RT (WBRT) up to 56 Gy in 2 Gy fractions (arm-B). Postoperatively, patients in arm-A with multifocality, lymphovascular invasion, nodal invasion, extensive intraductal component, invasive lobular carcinoma, or resection margins <1 cm received additional postoperative WBRT. RESULTS: Between 2002 and 2012, 184 patients were randomized, of whom 90 in arm-A and 90 in arm-B were evaluated. Median follow-up was 8.5 years. The 5­year overall survival was 94.4% in arm-A and 93.3% in arm-B (p = 0.73). Two local recurrences were observed: one at 70.3 months in an arm-A patient who received IORT + WBRT and another at 4.5 months in an arm-B patient who refused all forms of adjuvant treatment, thus resulting in a 5-year local recurrence of 0% in arm-A and 1.1% in arm-B. The 5­year in-breast recurrence (outside of the index quadrant) was 0% in arm-A and 1.2% in arm-B. Salvage mastectomy was performed successfully in all patients with relapse. CONCLUSION: Long-term follow-up of this single-center cohort consolidates the earlier reports of low local recurrence rates after single-dose IORT. Our results are in line with non-inferiority of risk-adapted IORT for selected patients with early breast cancer.

Vancomycin-induced Kounis Syndrome.

Kounis Syndrome is a rare allergic reaction that results in coronary vasospasm and may occur in patients with and without coronary artery disease. A 57-year-old man receiving pre-operative vancomycin for osteomyelitis and gangrene of the foot experienced an episode of anginal symptoms associated with transient ischemic 12-lead electrocardiogram (ECG) changes. The patient's symptoms and ECG changes abated with discontinuation of vancomycin and subsequent coronary angiography revealed no evidence of coronary artery disease. Treatment of Kounis Syndrome begins with cessation of the causative agent. Consensus guidelines for the management of Kounis Syndrome have not been established but treatment should both dilate the coronary vessels and suppress the allergic response. Coronary vasospasm after administration of antibiotics, including vancomycin, is a rare but serious reaction. It is important that Emergency Physicians recognize Kounis Syndrome as an uncommon yet dramatic and consequential reaction to such a commonly-administered antibiotic.

Quality assurance guidelines for superficial hyperthermia clinical trials : II. Technical requirements for heating devices.

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical trials with uniform quality hyperthermia treatments. This document outlines the requirements for appropriate QA of all current superficial heating equipment including electromagnetic (radiative and capacitive), ultrasound, and infrared heating techniques. Detailed instructions are provided how to characterize and document the performance of these hyperthermia applicators in order to apply reproducible hyperthermia treatments of uniform high quality. Earlier documents used specific absorption rate (SAR) to define and characterize applicator performance. In these QA guidelines, temperature rise is the leading parameter for characterization of applicator performance. The intention of this approach is that characterization can be achieved with affordable equipment and easy-to-implement procedures. These characteristics are essential to establish for each individual applicator the specific maximum size and depth of tumors that can be heated adequately. The guidelines in this document are supplemented with a second set of guidelines focusing on the clinical application. Both sets of guidelines were developed by the European Society for Hyperthermic Oncology (ESHO) Technical Committee with participation of senior Society of Thermal Medicine (STM) members and members of the Atzelsberg Circle.

Risk of Acute Kidney Injury After Intravenous Contrast Media Administration.

STUDY OBJECTIVE: The study objective was to determine whether intravenous contrast administration for computed tomography (CT) is independently associated with increased risk for acute kidney injury and adverse clinical outcomes. METHODS: This single-center retrospective cohort analysis was performed in a large, urban, academic emergency department with an average census of 62,179 visits per year; 17,934 ED visits for patients who underwent contrast-enhanced, unenhanced, or no CT during a 5-year period (2009 to 2014) were included. The intervention was CT scan with or without intravenous contrast administration. The primary outcome was incidence of acute kidney injury. Secondary outcomes included new chronic kidney disease, dialysis, and renal transplantation at 6 months. Logistic regression modeling and between-groups odds ratios with and without propensity-score matching were used to test for an independent association between contrast administration and primary and secondary outcomes. Treatment decisions, including administration of contrast and intravenous fluids, were examined. RESULTS: Rates of acute kidney injury were similar among all groups. Contrast administration was not associated with increased incidence of acute kidney injury (contrast-induced nephropathy criteria odds ratio=0.96, 95% confidence interval 0.85 to 1.08; and Acute Kidney Injury Network/Kidney Disease Improving Global Outcomes criteria odds ratio=1.00, 95% confidence interval 0.87 to 1.16). This was true in all subgroup analyses regardless of baseline renal function and whether comparisons were made directly or after propensity matching. Contrast administration was not associated with increased incidence of chronic kidney disease, dialysis, or renal transplant at 6 months. Clinicians were less likely to prescribe contrast to patients with decreased renal function and more likely to prescribe intravenous fluids if contrast was administered. CONCLUSION: In the largest well-controlled study of acute kidney injury following contrast administration in the ED to date, intravenous contrast was not associated with an increased frequency of acute kidney injury.

Quality assurance guidelines for superficial hyperthermia clinical trials: I. Clinical requirements.

Quality assurance guidelines are essential to provide uniform execution of clinical trials and treatment in the application of hyperthermia. This document provides definitions for a good hyperthermia treatment and identifies the clinical conditions where a certain hyperthermia system can or cannot adequately heat the tumour volume. It also provides brief description of the characteristics and performance of the current electromagnetic (radiative and capacitive), ultrasound and infra-red heating techniques. This information helps to select the appropriate heating technique for the specific tumour location and size, and appropriate settings of the water bolus and thermometry. Finally, requirements of staff training and documentation are provided. The guidelines in this document focus on the clinical application and are complemented with a second, more technical quality assurance document providing instructions and procedure to determine essential parameters that describe heating properties of the applicator for superficial hyperthermia. Both sets of guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.

Case Series: Pneumorrhachis Secondary to Spontaneous Pneumomediastinum.

BACKGROUND: Pneumorrhachis (PR) describes the clinical finding of air within the spinal canal and rarely has been associated with spontaneous pneumomediastinum. There is little medical literature addressing the evaluation and management of these patients in the emergency department. CASE REPORT: We present a series of patients with PR secondary to a spontaneous pneumomediastinum and briefly review the available literature on the topic to discuss reasonable management strategies for patients presenting with this rare finding. In both cases, the patients had excellent outcomes with expectant management despite the worrisome finding of air in the spinal canal. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians must be able to promptly recognize and appropriately assess even uncommon pathology. As with other rare conditions, there are no published guidelines for the ED management of PR, necessitating the use of case presentations to educate providers as to the complications and plan of care of this diagnosis.

Accelerating total body irradiation with large field modulated arc therapy in standard treatment rooms without additional equipment.

PURPOSE: The aim of this study was to develop a generic and ultra-efficient modulated arc technique for treatment with total body irradiation (TBI) without additional equipment in standard treatment rooms. METHODS: A continuous gantry arc between 300° and 70° composed of 26 subarcs (5° per subarc) using a field size of 40 × 40 cm(2) was used to perform the initial beam data measurements. The profile was measured parallel to the direction of gantry rotation at a constant depth of 9 cm (phantom thickness 18 cm). Beam data were measured for single 5° subarcs, dissecting the individual contribution of each subarc to a certain measurement point. The phantom was moved to 20 measurement positions along the profile. Then profile optimization was performed manually by varying the weighting factors of all segments until calculated doses at all points were within ± 1 %. Finally, the dose distribution of the modulated arc was verified in phantom thicknesses of 18 and 28 cm. RESULTS: The measured profile showed a relative mean dose of 99.7 % [standard deviation (SD) 0.7 %)] over the length of 200 cm at a depth of 9 cm. The measured mean effective surface dose (at a depth of 2 cm) was 102.7 % (SD 2.1 %). The measurements in the 28 cm slab phantom revealed a mean dose of 95.9 % (SD 2.9 %) at a depth of 14 cm. The mean dose at a depth of 2 cm was 111.9 % (SD 4.1 %). Net beam-on-time for a 2 Gy fraction is approximately 8 min. CONCLUSION: This highly efficient modulated arc technique for TBI can replace conventional treatment techniques, providing a homogeneous dose distribution, dosimetric robustness, extremely fast delivery, and applicability in small treatment rooms, with no need for additional equipment.

Dosimetric benefits of adaptive radiation therapy for patients with stage III non-small cell lung cancer.

BACKGROUND: Daily adaptive radiation therapy (ART) of patients with non-small cell lung cancer (NSCLC) lowers organs at risk exposure while maintaining the planning target volume (PTV) coverage. Thus, ART allows an isotoxic approach with increased doses to the PTV that could improve local tumor control. Herein we evaluate daily online ART strategies regarding their impact on relevant dose-volume metrics. METHODS: Daily cone-beam CTs (1 × n = 28, 1 × n = 29, 11 × n = 30) of 13 stage III NSCLC patients were converted into synthetic CTs (sCTs). Treatment plans (TPs) were created retrospectively on the first-fraction sCTs (sCT1) and subsequently transferred unaltered to the sCTs of the remaining fractions of each patient (sCT2-n) (IGRT scenario). Two additional TPs were generated on sCT2-n: one minimizing the lung-dose while preserving the D95%(PTV) (isoeffective scenario), the other escalating the D95%(PTV) with a constant V20Gy(lungipsilateral) (isotoxic scenario). RESULTS: Compared to the original TPs predicted dose, the median D95%(PTV) in the IGRT scenario decreased by 1.6 Gy ± 4.2 Gy while the V20Gy(lungipsilateral) increased in median by 1.1% ± 4.4%. The isoeffective scenario preserved the PTV coverage and reduced the median V20Gy(lungipsilateral) by 3.1% ± 3.6%. Furthermore, the median V5%(heart) decreased by 2.9% ± 6.4%. With an isotoxic prescription, a median dose-escalation to the gross target volume of 10.0 Gy ± 8.1 Gy without increasing the V20Gy(lungipsilateral) and V5%(heart) was feasible. CONCLUSIONS: We demonstrated that even without reducing safety margins, ART can reduce lung-doses, while still reaching adequate target coverage or escalate target doses without increasing ipsilateral lung exposure. Clinical benefits by means of toxicity and local control of both strategies should be evaluated in prospective clinical trials.